(4S)-4-amino-5-[[(2S)-1-[[(2S)-3-carboxy-1-[[(4S,5S,7R)-8-[[(2S)-1-[[(2S)-4-carboxy-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-hydroxy-2,7-dimethyl-8-oxooctan-4-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid | 452898-62-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (4S)-4-amino-5-[[(2S)-1-[[(2S)-3-carboxy-1-[[(4S,5S,7R)-8-[[(2S)-1-[[(2S)-4-carboxy-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-hydroxy-2,7-dimethyl-8-oxooctan-4-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid
• CAS: 452898-62-3
• 化学式: C₄₄H₆₉N₇O₁₅
• 分子量: 936.07
• InChiKey: CFIWWTUUSMMDDA-IQRKPKHNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  66
• 可旋转键数：
  31
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  370
• 氢给体数：
  12
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  、 Fmoc-L-缬氨酸 、 Fmoc-L-亮氨酸 、 (2R,4S,5S)-5-amino-4-hydroxy-2,7-dimethyloctanoic acid 、 Fmoc-L-天冬氨酸 、 Fmoc-L-谷氨酸 在 哌啶 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (4S)-4-amino-5-[[(2S)-1-[[(2S)-3-carboxy-1-[[(4S,5S,7R)-8-[[(2S)-1-[[(2S)-4-carboxy-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-hydroxy-2,7-dimethyl-8-oxooctan-4-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  Peptidomimetic β-Secretase Inhibitors Comprising a Sequence of Amyloid-β Peptide for Alzheimer’s Disease

  摘要：

  Alzheimer's disease is a grave social problem in an aging population. A major problem is the passage of drugs through the blood brain barrier. This work tests the hypothesis that the conjugation of peptidomimetic beta-secretage inhibitors with a fragment of amyloid-beta peptide facilitates entrance into the central nervous system. HVR-3 (compound 4), one of the conjugation products, was found to be as potent as OM00-3, a known peptidomimetic inhibitor, 4-fold more selective toward beta-secretase 1 in relation to beta-secretase 2 and 3-fold more resistant to in vitro metabolization in human serum. Its intravenous administration to mice and Wistar rats generated an active metabolite recovered from the rodent's brains.

  DOI：

  10.1021/acs.jmedchem.5b00658

文献信息

• BRAIN PERMEANT PEPTIDOMIMETIC BETA-SECRETASE 1 INHIBITORS FOR THE TREATMENT OR PROPHYLAXIS OF NEUROLOGICAL DISORDERS OR CONDITIONS
  申请人：IBET - INSTITUTO DE BIOLOGIA EXPERIMENTAL E TECNOLOGICA

  公开号：US20170296618A1

  公开（公告）日：2017-10-19

  The present application presents novel peptidomimetic substituted hydroxyethylene compounds, which are inhibitors of beta amyloid cleavage enzyme, capable to permeate the brain and to achieve therapeutic concentrations in the target organ, the brain. These compounds are incorporated in pharmaceutical compositions and applied in the treatment or prophylaxis of neurological disorders or conditions and also other disorders or conditions including Down's syndrome and diabetes.

  这项申请提出了一种新型的肽类模拟替代羟基乙烯化合物，这些化合物是β淀粉样蛋白裂解酶的抑制剂，能够渗透到大脑并在目标器官大脑中达到治疗浓度。这些化合物被纳入药物组合物中，并应用于治疗或预防神经系统疾病或症状以及其他疾病或症状，包括唐氏综合征和糖尿病。
• US9919021B2
  申请人：——

  公开号：US9919021B2

  公开（公告）日：2018-03-20
• Peptidomimetic β-Secretase Inhibitors Comprising a Sequence of Amyloid-β Peptide for Alzheimer’s Disease
  作者：Helder Vila-Real、Helena Coelho、João Rocha、Adelaide Fernandes、M. Rita Ventura、Christopher D. Maycock、Olga Iranzo、Ana L. Simplício

  DOI：10.1021/acs.jmedchem.5b00658

  日期：2015.7.23

  Alzheimer's disease is a grave social problem in an aging population. A major problem is the passage of drugs through the blood brain barrier. This work tests the hypothesis that the conjugation of peptidomimetic beta-secretage inhibitors with a fragment of amyloid-beta peptide facilitates entrance into the central nervous system. HVR-3 (compound 4), one of the conjugation products, was found to be as potent as OM00-3, a known peptidomimetic inhibitor, 4-fold more selective toward beta-secretase 1 in relation to beta-secretase 2 and 3-fold more resistant to in vitro metabolization in human serum. Its intravenous administration to mice and Wistar rats generated an active metabolite recovered from the rodent's brains.